The Dual Role of Calcium as Messenger and Stressor in Cell Damage, Death, and Survival

Figure 2

Capacitative and noncapacitative Ca²⁺ entry. Ligand (L) stimulation of G-protein (α βγ)-coupled receptor (R) activates phospholipase C (PLC) to produce diacylglycerol (DAG) and inositol-3-phosphate (IP₃). IP₃ (right side) causes ER Ca²⁺ emptying, eliciting a capacitative Ca²⁺ entry (CCE) through plasma membrane (PM), aimed at refilling ER of Ca²⁺ restoring ER homeostasis. DAG (left side) is processed to arachidonic acid (AA) by DAG lipase (DAGL), stimulating NOS to produce NO, which activates Ca²⁺ entry through PM by a noncapacitative Ca²⁺ entry (NCCE), priming specific signaling including anti-apoptotic pathways. CCE and NCCE differ in protein composition [124]. Red dots symbolize Ca²⁺.